Target nature :
TrkB
CAS n° :
219766-25-3
Mecanism of action :
negative allosteric modulator
Physico-chemical properties :
Molecular mass: 407.49 AlogP: 3.08 Topological surface area (tPSA): 115 Solubility in DMSO: >=5 mg/mL at 60 °C
Probe availability :
The probe is available at several commercial suppliers: Alomone Labs (#A-215), Sigma-Aldrich (SML0209-5MG), Tocris (Cat. No. 4781), Abcam (ab146196), SelleckChem (S7745),
Princeps reference :
Cazorla, M., Prémont, J.,Mann, A., Girard, N., Kellendonck, C. and Rognan, D. (2011) Virtual screening identifies a low molecular-weight TrkB antagonist with anxiolytic and antidepressant potential in rodents. J. Clin. Invest., 121, 1846-1857
More bibliography :
132 bibliographic references at https://www.ncbi.nlm.nih.gov/pubmed/?term=ANA-12
Other available information on the probe :
storage at 4-10°C
Other information on the target :
Trkb is a receptor tyrosine kinase whose endogenesous ligand is BDNF (Brain-derived neurotrophic factor). TrkB activation by BDNF plays a major role in neuronal homeostasis (growth, proliferation, survival). Its activity is altered in many CNDS diseases (anxiety, depression, epilespy, neurodegenerative diseases, cancer) for more details see: Longo FM, Massa SM (2013) Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease. Nat Rev Drug Discov. 12:507-525.
Selectivity profile :
selective vs. TrKA and TrkB (neurite outgrowth)
In vivo data :
antidepressant (forced swim test, tail suspension test) and anxiolytic (elevated plus maze) after 0.5 mg/kg i.p. administration in mice
In vitro data :
- IC50 = 45 nM (KIRA ELISA on cortical neurons) Inhibition of BDNF-induced neurite outgrowth in nnr5-PC12-TrkB cells
Toxicity :
no toxicity in rodents, no modification of the locomotor activity
Chaine SMILES :
O=C(Nc1ccccc1C(=O)NC2CCCCNC2=O)c4cc3ccccc3s4
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